The origin of the "ideal" body weight equations.

OBJECTIVE: To provide a historical perspective on the origin and similarity of the "ideal" body weight (IBW) equations, and clarify the terms ideal and lean body weight (LBW). DATA SOURCES: Primary and review literature were identified using MEDLINE (1966-November 1999) and International Pharmaceutical Abstracts (1970-November 1999) pertaining to ideal and lean weight, height-weight tables, and obesity. In addition, textbooks and relevant reference lists were reviewed. DATA EXTRACTION: All articles identified through the data sources were evaluated. Information deemed to be relevant to the objectives of the review were included. DATA SYNTHESIS: Height-weight tables were generated to provide a means of comparing a population with respect to their relative weight. The weight data were found to correlate with mortality and resulted in the use of the terms desirable or ideal to describe these weights. Over the years, IBW was interpreted to represent a "fat-free" weight and thus was used as a surrogate for LBW. In addition, the pharmacokinetics of certain drugs were found to correlate with IBW and resulted in the use of IBW equations published by Devine. These equations were consistent with an old rule that was developed from height-weight tables to estimate IBW. Efforts to improve the IBW equations through regression analyses of height-weight data resulted in equations similar to those published by Devine. CONCLUSIONS: The similarity between the IBW equations was a result of the general agreement among the various height-weight tables from which they were derived. Therefore, any one of these equations may be used to estimate IBW.

Aggressive approach in the treatment of acute lead encephalopathy with an extraordinarily high concentration of lead.

OBJECTIVE: To report a case of a 3-year-old child with an extraordinarily massive lead concentration, 26.4 micromol/L (550 microg/dL), following environmental exposure to lead paint in the home. LITERATURE REVIEW: The relevant literature concerning the treatment of lead encephalopathy was reviewed during the treatment of this child and preparation of the manuscript. To our knowledge, the landmark article written by Julian Chisolm in 1968 is the only recent article that reported similarly high levels of lead concentration. This case, however, is the first in which 3 chelating agents were used for the treatment of lead encephalopathy. We also reviewed the literature on the use of whole bowel irrigation in heavy metal intoxications. CONCLUSIONS: In this case, aggressive gut decontamination with whole bowel irrigation and triple chelation therapy with British anti-Lewisite, EDTA, and oral succimer was well tolerated and seemed effective for rapidly deleading the child. The extent to which her lead concentration increased while being treated with oral succimer alone necessitated further chelation with EDTA. Further evaluation is necessary to determine if triple chelation therapy is an appropriate method for severe lead intoxication, and if the use of whole bowel irrigation should be considered in heavy metal intoxication.

Prediction of acetaminophen concentrations in overdose patients using a Bayesian pharmacokinetic model.

A pharmacokinetic program using population-based parameter estimates and a Bayesian forecasting model was retrospectively evaluated for predicting acetaminophen serum concentrations in overdose patients. Dynamic disposition factors known to affect acetaminophen disposition (emesis, activated charcoal, N-acetylcysteine, etc.) were included in the program. Twenty six patients who reported an acetaminophen ingestion of at least 70 mg/kg within 24 h of presentation to the hospital and had at least one measured acetaminophen concentration were included. Prediction of initial acetaminophen concentrations using only population-based parameter estimates resulted in a percent mean error (%ME) and percent mean absolute error (%MAE) of 9.3 and 42.2, respectively. Using only the initial concentration as feedback, the Bayesian forecasting model accurately predicted the second acetaminophen concentration (%ME = 4.0, %MAE = 23.6). The Bayesian model also accurately predicted all concentrations within 8 h of the ingestion (%ME = 10.6, %MAE = 24.0). The prediction of concentrations between 2 to 4 h and 4 to 4.5 h after ingestion with only population-based parameter estimates resulted in %ME of 17.0 and 13.2, respectively, and %MAE of 36.5 and 35.1, respectively. Our data suggests that acetaminophen serum concentrations occurring within the first 4.5 h after ingestion can be reliably predicted by the set of population-based parameter estimates evaluated. Once a single acetaminophen concentration is available, the Bayesian forecasting model can accurately predict subsequent concentrations within the first 8 h after an acetaminophen ingestion.

Metered-dose inhalers and nebulizers in the acute setting.

OBJECTIVE: This article evaluates the current literature comparing beta-adrenergic agonists administered via metered-dose inhalers (MDIs) with nebulizer devices in adult and pediatric patients. These studies focus on the acute treatment of asthma or chronic obstructive pulmonary disease in the emergency department and other acute care settings. DATA SOURCES: English-language journal articles published between 1980 and 1991. STUDY SELECTION: Eight studies that compared beta-adrenergic agonists administered via an MDI or an MDI with a spacing device versus a nebulizer were identified. All of the studies were either poorly designed or had few subjects. By consensus of the authors, all were included in the review. DATA EXTRACTION: Studies were assessed according to methodologic strength (e.g., prospective, comparative). DATA SYNTHESIS: Five studies found no differences between administration methods, one study found metered-dose inhalation to be superior, and another found nebulization to be superior based on observed improvements in pulmonary function tests. There were no significant differences in adverse-reaction rates. When surveyed, subjects preferred MDIs to nebulizers. There were marked variations in doses administered within and between studies. There was no consideration given to doses potentially delivered to the lungs. CONCLUSIONS: There is no significant difference between nebulizers and MDIs plus a spacer with regard to the administration of beta-agonists in the treatment of acute asthma. There are insufficient data to conclusively support the role of spacers in this setting. The choice of a specific delivery method at this time must be determined on an individual basis, taking into account the issues of cost, timeliness of administration, and personnel availability.

Assessment and treatment of acetaminophen overdose.

The assessment and treatment of acute acetaminophen toxicity are reviewed, and several unresolved issues are discussed. The drug most commonly involved in analgesic ingestions, as a single agent or in combination, is acetaminophen. Hepatotoxicity, the major manifestation of acetaminophen ingestion, is believed to result from the accumulation of a toxic metabolite, N-acetylimidoquinone. The clinical features of acetaminophen toxicity are divided into four stages ranging from minor symptoms, such as gastrointestinal irritation, to coma and death. The most reliable method for assessing the severity of acetaminophen ingestion is comparison of serum acetaminophen concentrations with the Rumack-Matthew nomogram. Delaying the start of antidotal therapy for more than 10 hours after the ingestion increases the risk of toxicity; no benefit is observed when antidotal therapy is initiated more than 24 hours after ingestion. Acetaminophen is often marked in combination with other drugs; a detailed patient history and a urine toxicology screen help determine whether multiple toxic ingestions have occurred. The roles of ipecac, gastric lavage, and activated charcoal in therapy are controversial. The mainstay of treatment for acetaminophen intoxication is a 17-dose course of acetylcysteine.

Evaluation of drug therapy for treatment of hypertensive urgencies in the emergency department.

Oral nifedipine (N) and clonidine (C) are often used in the treatment of hypertensive urgencies; however, until recently, there were no comparative studies using the same patient population. The authors reviewed the records of hypertensive patients treated in the emergency department between October 1, 1987 and September 30, 1988. Selected patients had a diastolic blood pressure (DBP) of greater than 115 mm Hg without evidence of acute end organ damage. Patients were stratified into three treatment groups: N, C, and group 3 (G3). G3 received a variety of drug therapies but not exclusively N or C. Systolic blood pressure (SBP), DBP, mean arterial pressure (MAP), percent decrease in MAP (%MAP), time to lower blood pressure, admissions, and discharges were evaluated. Efficacy and safety were defined as reaching a DBP less than 110 mm Hg but %MAP of no greater than either 25% or 40%, respectively. Thirty-five N, 32 C, and 27 G3 patients were identified with no statistical difference between groups in race, gender, pretreatment SBP, DBP, or MAP. N, C, and G3 significantly reduced SBP, DBP, and MAP (P less than .01). Comparing N, C, and G3, no differences were observed in %MAP, admissions, discharges, efficacy, or safety. Time required to decrease blood pressure differed between all three groups (44 +/- 32 N v 77 +/- 57 C v 152 +/- 94 min G3) (p less than .05). These results indicate that N, C, and a variety of drug therapies are equally effective and safe in the treatment of hypertensive urgencies.

Effect of food on the serum concentration profile of enteric-coated valproic acid.

We evaluated the effect of food on the serum concentration profile of enteric-coated divalproex sodium (EC-VPA) in six adult volunteers following a single dose and in six patients during chronic-dose administration. The results demonstrated a significant delay but no decrease in extent of EC-VPA absorption following administration with food. To monitor serum concentrations in patients receiving EC-VPA, consideration of sampling time in relation both to time of dose and meals is required.

Evaluation of theophylline overdoses and toxicities.

Patients presenting with elevated theophylline concentrations and manifestations of toxicity may be categorized as being either overdose or iatrogenic toxic. In addition to severe cardiac and neurologic toxicities, such as arrhythmias and seizures, OD patients probably require monitoring for manifestation of gastrointestinal hemorrhage, electrolyte abnormalities, and hypotension. The possibility of a delayed peak theophylline concentration after sustained release product ingestion must be considered. Patients with initial serum concentrations of less than 60 mg/L may receive a single dose of oral activated charcoal and have repeat concentrations drawn to ensure the avoidance of continued absorption. The presence of a serum concentration exceeding 60 mg/L in OD patients warrants initiation of elimination-enhancing modalities. Oral activated charcoal is the fastest and most readily available. Multiple-dose oral activated charcoal should be given until serum theophylline concentrations of 60 mg/L or less are reached. Cardiac monitoring and seizure precautions are recommended. Admission to the intensive care unit should be considered when serum concentrations do not decline after several hours of charcoal therapy or when seizures and severe cardiovascular manifestations occur. Patients having initial concentrations exceeding 100 mg/L and/or rapidly rising concentrations 100 mg/L over baseline values should be considered as candidates for CHP or RHP if available. If both CHP and RHP are unavailable or will be excessively delayed, HD is a reasonable alternative. Patients on chronic theophylline therapy (IA patients) presenting with symptoms of toxicity must be evaluated carefully. If serum concentrations are less than 20 mg/L, short-term observation or a reduction in dose should be sufficient. Patients with concentrations between 20 and 60 mg/L should be candidates for seizure precautions and cardiac monitoring. Oral activated charcoal may be started and continued until levels are below 20 mg/mL. Patients with concentrations in excess of 60 mg/L require intensive monitoring (including seizure precautions and cardiac monitoring) as well as initiation of MOAC or CHP/RHP as situation, availability, and patient tolerance dictate. Again, HD may be a reasonable alternative if the others are unavailable or contraindicated.

Interaction of steady-state procainamide with H2-receptor antagonists cimetidine and ranitidine.

This study was designed to compare the effects of equivalent therapeutic doses of two H2 antagonists, cimetidine and ranitidine, on steady-state procainamide pharmacokinetics. Six healthy men were given 500 mg sustained-release procainamide every 6 h, for a total of 13 doses, on three occasions. Subjects were randomly assigned to three treatments by a Latin-square design: cimetidine 1,200 mg/day, ranitidine 300 mg/day, and no H2-receptor antagonist (control) for 4 days. Cimetidine significantly increased the procainamide area under the serum concentration-time curve by 43%, decreased renal clearance by 36%, and decreased the ratio of systemic clearance of procainamide to bioavailability by 28%. Ranitidine did not significantly alter procainamide steady-state pharmacokinetics.

Evaluation of topical metronidazole gel in acne rosacea.

Topical metronidazole gel (0.75%) was compared to placebo gel in a randomized, double-blind, placebo-controlled, split-face clinical trial for the treatment of 59 patients with acne rosacea. Statistically significant differences in inflammatory lesions, erythema, and global assessments were seen at three, six, and nine weeks post-baseline in favor of the active treatment side. It did not, however, alter the telangiectatic component of the disease. No known drug-related side effects were detected, and the low topical dose along with low serum levels of metronidazole indicate a high safety profile for this therapeutic agent. This work suggests that metronidazole gel, as specifically formulated, is safe and effective in reducing the symptomatology of acne rosacea.

Accuracy of 11 methods for predicting theophylline dose.

Eleven methods for pharmacokinetic determination of theophylline dose were compared, based on the ability of each method to predict theophylline serum concentration and clearance for adults with asthma. Predictions by each method were compared with actual serum theophylline concentrations before and after an aminophylline loading dose was administered to treat bronchospasm in 22 patients. Follow-up serum theophylline concentrations were obtained after maintenance therapy with i.v. aminophylline in 6 patients and an oral sustained-release theophylline product (Theo-Dur, Key) in 16 patients; maintenance doses administered to the patients were calculated by the method of Chiou et al. Two variations of the method of Chiou et al., seven Bayesian methods using one or more measured serum theophylline concentrations, FDA's standardized clearance estimate, and a population-based clearance-estimation method were compared. A one-compartment, open model with first-order elimination was assumed for all calculations. All 11 methods predicted steady-state concentration with minimal bias and good precision. The Chiou and Bayesian methods performed similarly, with the highest precision found for the Bayesian method that incorporated four measured concentrations. The population-based method had the highest correlation coefficient and the lowest mean error for predicting steady-state concentration. Decreasing the number of measured concentrations had a minimal effect on the various Bayesian methods. All methods evaluated are sufficiently accurate for clinical application in patients with stable, uncomplicated asthma.

Postmenopausal vaginal bleeding during estrogen therapy.

PIP: Opinions on whether dilatation and curettage is justified in the case of vaginal bleeding in postmenopausal women taking estrogens are presented. Postmenopausal bleeding induced by estrogens usually stops after cessation of treatment, while bleeding due to endometrial cancer usually recurs or continues after cessation of estrogen therapy. Since endometrial cancer may become "silent" after initial bleeding, dilatation and curettage is indicated in all cases of postmenopausal vaginal bleeding, irregardless of estrogen therapy.^ieng